INSR and type 2 diabetes mellitus: Previous studies showed that JNK pathway was activated by ER stress in animal models of obese (Liang et al., 2015) and T2DM (Sims-Robinson et al., 2012), resulting in impaired insulin receptor signaling in the hippocampus and cortex, exhibiting an increased activity of GSK3β and Tau hyperphosphorylation (Chiu and Cline, 2010; Barbagallo and Dominguez, 2014; Ma et al., 2014).